孟德尔随机化
格尔德
回流
冲程(发动机)
疾病
医学
观察研究
心脏病学
全基因组关联研究
内科学
调解
遗传学
生物
基因
单核苷酸多态性
遗传变异
机械工程
基因型
工程类
法学
政治学
作者
Shixuan Chen,Zhenzhen Chen,Xia Jiang,Chuyong Lin,Jing Ji
标识
DOI:10.1016/j.jstrokecerebrovasdis.2024.107612
摘要
Abstract
Objectives
Previous observational studies have suggested that gastroesophageal reflux disease (GERD) increases the risk of stroke, but the specific underlying mechanisms are unclear. We investigated the causal associations of GERD with stroke and its subtypes using Mendelian randomization (MR), and evaluated the potential mediating effects of modifiable stroke risk factors in the causal pathway. Methods
Genetic instrumental variables for GERD were extracted from the latest genome-wide association study (GWAS) summary level data. We initially performed two-sample MR to examine the association of GERD with stroke and its subtypes, including ischemic stroke, intracranial hemorrhage, and the major subtypes of ischemic stroke. Two-step MR was further employed to investigate the mediating effect of 15 risk factors in the causal pathway. Results
We found significant causal associations of genetically predicted GERD with increased risk of stroke (OR: 1.22 95% CI: 1.126–1.322), ischemic stroke (OR: 1.19 95% CI: 1.098–1.299), and large-artery stroke (OR: 1.49 95% CI: 1.214–1.836). Replication and sensitivity analyses yielded consistent effect directions and similar estimates. Further mediation analyses indicated that hypertension (HTN), systolic blood pressure (SBP), and type 2 diabetes (T2D) mediated 36.0%, 9.0%, and 15.8% of the effect of GERD on stroke; 42.9%, 10.8%, and 21.4% for ischemic stroke, and 23.3%; 7.9%, and 18.7% for large-artery stroke, respectively. Conclusions
This study supports that GERD increases susceptibility to stroke, ischemic stroke, and large-artery stroke, and is partially mediated by HTN, SBP, and T2D.
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